Non-invasive spectrophotometer

ABSTRACT

A device for use in non-invasive monitoring of a human or animal subject&#39;s bodily functions in vivo, comprises:
         a first optical system for identifying the center ( 1 ) of a pupil ( 13 ) of an eye of the subject, said first system comprising a first light source ( 2 ) for directing light towards the eye, first receiving means for receiving light reflected from the iris ( 4 ) of the eye, and first processing means for determining the position of the center ( 1 ) of the pupil ( 13 ) from the light reflected ( 3 ) from the iris;   a second optical system comprising a second light source ( 14 ) directing light to a focussing means ( 15 ) for focussing light in the plane of the pupil ( 13 ) and for directing the focussed light onto the retina ( 10 ) of the eye, a second receiving means for receiving light reflected ( 17 ) from the retina and back through the pupil ( 13 ), and second processing means for analyzing the light reflected from the retina ( 10 ); and   alignment means for aligning the second system with the center ( 1 ) of the pupil ( 13 ) as determined by the first system.

This application is the U.S. national phase of international applicationPCT/GB02/01083 filed 8 Mar. 2002, which designated the U.S.

FIELD OF THE INVENTION

The present invention relates to a device for use in non-invasivemonitoring of a human or animal subject's bodily functions in vivo. Thedevice relates, more particularly, to such monitoring that uses lightbeams directed at, and reflected from, various parts of the subject'seye(s) to provide analysable data.

Monitoring the functions of a human or animal body is necessary in manydifferent situations. In the past, blood sample gave been taken from thepatient or animal and constituents have been measured byspectrophotometry. It is also known to relatively invasively measure theconstituents in the blood of the patient or of the animal by bringingthe spectrophotometer into contact with the patient or the animal, byfor example using modified contact lens systems. The eye, which is theonly part of the body that is designed to transmit light, thus acts asthe curvette for the spectrophotometer.

BACKGROUND ART

The use of spectrophotometric techniques for monitoring the level andvariation of one or more parameters indicative of body condition is wellknown. Thus, U.S. Pat. Nos. 4,157,708 and 4,402,325 disclose ophthalmicdevices incorporating one or more plethysmograph assemblies, but thesedevices have the disadvantage that light is assumed to be introducedalong the axis of the pupil of the subject's eye.

In addition, U.S. Pat. Nos. 5,553,617 and 5,919,132 describe furthernon-invasive methods of measuring body conditions but, again, lightintroduced into the eye is assumed to be directed along the axis of thepupil.

SUMMARY OF THE INVENTION

It is therefore a first aim of the present invention to overcome thedisadvantages of the prior art by providing a non-invasivespectrophotomeric system, which ensures that light, used to monitor thebody condition of a subject, is directed along the axis of the eye bybeing focused in the centre of the plane of the iris, which is otherwiseknown as being the Maxwellian view of the pupil.

It is a second aim of the present invention to provide such a systemthat minimises the potential injury to the iris and other structures ofthe eye, should light (used for spectrophotometric analysis) not bedirected through the pupil in Maxwellian view, thus overcoming anotherdisadvantage of the prior art.

A third aim of the present invention is to allow measurement of theamount of light illuminating the eye by focusing the light in Maxwellianview.

Thus, in a first aspect, the present invention provides a device for usein non-invasive monitoring of a human or animal subject's bodilyfunctions in vivo, comprising:

-   -   (a) a first optical system for identifying the centre of a pupil        of an eye of the subject, said first system comprising a first        light source for directing light towards the eye, first        receiving means for receiving light reflected from the iris of        the eye, and first processing means for determining the position        of the centre of the pupil from the light reflected from the        iris;    -   (b) a second optical system comprising a second light source        directing light to a focusing means for focusing light in the        plane of the pupil and for directing the focused light onto the        structures within the eye, a second receiving means for        receiving light structures from the structure and back through        the pupil, and second processing means for analysing the light        reflected from the structure; and    -   (c) alignment means for aligning the second system with the        centre of the pupil as determined by the first system.

The device therefore comprises at least three major components.

The first major component the first optical system, is preferablyprovided by modifying a standard pupillometer, such as that described inU.S. Pat. No. 5,784,145. Further, the general principles of usingpupillometry in this context are described in the applicant's previousInternational Patent Application No. WO/90/12534.

The second major component, that is the second optical system, isusually provided by modifying a standard spectrophotometer and thegeneral principles of using such spectrophotometric techniques are againdescribed in the applicant's prior International Patent Application No.WO/90/12534. A typical example of the type of structure within the eyeonto which light is focused is the retina. In the spectroscopy field,the eye is in effect the curvette of the body, since it is the only partof the body that is designed to transmit light. Thus, measurement of thecharacteristics of light reflected from the eye can give an indicationof characteristics of bodily functions in general.

Typically, the third major component, that is the alignment means, iscontrollable either directly by, or independently of, the subject, forexample by use of manually operated lever(s), button(s), joystick(s)and/or one or more computer mice. The alignment means provides' avariable focus capability to the system and may optionally operate in anautomatic way without personal intervention from either the subject orthe clinician. Indeed, activation of such alignment may also beautomatically initiated by the first optical system, once the centre ofthe pupil in Maxwellian view has been determined.

In one embodiment, the device is arranged to project an image processedby the first processing means onto the retina of the operator (whetherthe subject or not), so as to allow the operator to be able to perceivewhen the position of the centre of the pupil has been determined and sobe able to operate the alignment means appropriately.

In addition, the device may be arranged to gather data from either aselected eye or from both eyes of the subject, that is, to be amonocular or binocular system.

Typically, the first light source emits infra-red light, for examplefrom one or more LED(s).

Preferably, the second receiving means comprises one or more crystalcharged device (ccd)-type camera(s).

In one embodiment, the first optical system is adapted to monitor, inparticular, the location of the edge(s) of the pupil(s), so as to allowcalculation of the centre of the pupil(s) by the first processing means.

Preferably, the first and second light sources comprise one or moreoptical fibre(s) for transmitting light towards the eye(s). In aparticularly preferred arrangement, the optical fibre(s) are arranged tofunction as both the light input means and the light receiving means.

In one embodiment the second light source and the second receivina meansare arranged to monitor the intensity of light of a selected wavelengthreturning from the retina(s) of the eye(s).

In an alternative embodiment, the second light source and secondreceiving means are arranged to monitor the intensity of light ofdifferent wavelengths returning from the retina(s) of the eye(s),thereby enabling an absorbance/reflectance characteristic of theretina(s) to be determined.

The first and second optical systems may have parts in common. Thus, forexample, the first and second receiving means can optionally be providedby the same unit. Likewise, the first and second processing means canalso be the same processing means, if desired.

The expression “human and bodily functions” used herein is intended toinclude the wide variety of different functions that a medical orveterinary practitioner may wish to non-invasively monitor or measure.In particular, it is intended to include the monitoring of anysubstances and changes in the blood of the retina and any biochemical(organic or inorganic) changes in the cells of the retina of thesubject. In addition, any or all of these changes can be monitored inconjunction with changes in the electrical, biochemical or pathologicalactivity of the retina or of the brain.

The term “light” used herein is, unless otherwise specified, intended toinclude visible wavelengths and non-visible wavelengths such asinfra-red and ultra-violet light, that are non-injurious to the eye andthe structures contained within the eye.

The present invention will now be described in further detail by way ofthe following non-limiting examples with reference to the drawings, inwhich:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic representation of the first optical system ofan embodiment of the present invention;

FIG. 2 illustrates an image of the eye on a computer screen, as may beused in one embodiment of the present invention; and

FIG. 3 shows a schematic representation of the second optical system ofan embodiment of the present invention.

BEST MODE

In FIG. 1, a first optical system is shown that is capable ofidentifying the centre 1 of a pupil of an eye of a subject. This firstsystem comprises a first light source 2 that directs light of aninfra-red wavelength towards the eye, a first receiving means (notshown) that receives fight subsequently reflected 3 from the iris 4 ofthe eye, and a first processing means (not shown) that then determinesthe position of the centre 1 of the pupil from the light 3 so reflectedfrom the iris 4.

Input light 5 is directed by one or a bundle of optical fibre(s) thatconstitute the first light source 2 and is emitted towards the eye. Thedevice is enclosed in a housing 12 and, depending upon alignment of thishousing 12, the focused light either passes through the pupil oralternatively is reflected by the iris 4. The latter light 11 isdirected back into the housing 12 of the device and passes as a beam 3of reflected light that can be detected by the first receiving means.Also shown in FIG. 1 are the anterior chamber 8 of the eye and the lens9 of the eye.

In FIG. 2, a Maxwellian view of the eye is shown on a computer screen 6,the view being a cross-sectional view of the eye about line A-A′ inFIGS. 1 and 3. The, iris 4 is illustrated surrounding the centre 1 ofthe pupil 13. A computer-processing unit 20 represents the first andsecond processing means and the first and second optical systems aredepicted as unit 19.

The first optical system is sequentially alignable with respect to theeye such that the first light source 2 directs infra red light eitherthrough the pupil 13 or onto the iris 4. Reflected light 11 from theiris forms a beam 3 that is analysed by the first processing means, sothat the centre 1 of the pupil 13 can be determined. Typically, thepixels of the image produced by the beam 3 are analysed to determine thelocation of the circumference of the circle represented by the edge ofthe iris 4. In one option, the radius of the circle is then calculatedby the first processing means, so that the location of the centre 1 canbe identified, however other methods of similar calculation are clearlypossible.

In FIG. 3, a second optical system is shown that comprises a secondlight source 14 directing light to a focusing means 15 for focusinglight in the plane of the pupil 13 and for directing the focused lightonto the retina 10 of the eye. A second receiving means (not shown)receives light 17 reflected from the retina 10 and back 16 through thepupil 13. A second receiving and processing means (not shown) isprovided for analysing the light 17 that is reflected from the retina 10and back through the pupil 13 into the housing 12 of the device.

Once the first optical system has been used to locate the centre 1 ofthe pupil 13, the alignment means (not shown) of the device can be usedto align the second optical light so that light is shone through thecentre 1 of the pupil 13 in the plane of the pupil 13, that is in aMaxwellian view. The alignment process can be effected by way of, forexample, a joystick (18) (see FIG. 2), which can be operated by thephysician, or the subject themselves. In this way, the operator can viewan image of the eye being investigated on a screen 6 and, inconjunction, use the joystick 18 to align the second optical system withthe centre 1 of the pupil 13.

However, the device may be arranged for example such that the firstoptical system operates automatically (i.e. without manual operation).Thus, the first optical system may directly activate the alignment meansto position the second optical system into the correct alignment withthe centre of the pupil, so as to provide a Maxwelllan view of the eye.

Further, instead of the operator viewing the image of the eye on ascreen, such an image may be transferred directly onto the retina of theoperator, for example by way of the second optical system itself.

As shown in FIG. 3, input light 14 is directed via an optical fibre fromwhich it is emitted so as to pass through a focusing means 15 and out ofthe housing 12 of the device towards the centre 1 of the pupil 13. Light16, which is reflected back from the retina 10 and back through thepupil 13, subsequently passes back into the device and travels as a beam17 along one or more optical fibres to the second processing means.

The second processing means analyses the beam 17 to determine theabsorbance/reflectance spectrum of the retinal blood supply. Anycombination of mono-chromatic lights or white light, as well aswavelengths in the infra-red or ultra-violet spectra can be used.Specific, selected wavelengths permit optimal discrimination of thevarious blood components, as well as optimal discrimination of thevarious retinal biochemical functions and components.

In this way, it is, for example, possible to provide an accuratemeasurement of the oxygen saturation of the retinal blood flow and,since this is more proximal to blood flow in the toe, finger or ear (asmeasured by well known prior techniques), it can provide the clinicianwith a more accurate assessment of the oxygen content of blood deliveredto the brain.

The system described above can be used for a wide range of applications.For example, it is possible to measure any, or all, of the constituentsof the blood of a subject, in vivo. Additionally, when appropriatewavelengths are used, it is also possible to measure the constituents ofthe cells of the retina or to measure physiological and or pathologicalchanges in the cells of the retina. It is possible to measure thebiochemical activity of these cells, in real time.

Further, it is possible also to use the system to measure the unique DNAprofile of any individual and thus provide security checks. For example,a monocular system can be used as part of a cash-dispensing machine, inwhich the identity of the person wishing to withdraw cash is checked vianon-invasive DNA analysis of the retinal cells.

Whereas police currently use breathalysers to check a driver's bloodalcohol levels at the road side, using the present system would not onlyallow such analysis to be more accurately performed, but would alsoallow analysis of any number of other drugs that can be detrimental todriving, which may also be present in a driver's blood.

Moreover, the system is also more suitable for monitoring the bloodglucose levels of diabetic patients than conventional needle-basedmethods, since it is non-invasive.

It is also possible to measure changes in the arteries and veins of theretina, which may be an indication of generalised arterial and venousdisease. Thus, in diabetic patients, who typically can suffer from suchgeneralised arterial disease, it would be possible to non-invasivelychart the progression of the disease.

Hence, in general, the system in effect provides the subject with theresources of a non-invasive, real time biochemical and haematologicallaboratory.

The system can measure visual evoked potentials more accurately thanconventional means, because it is possible to give an accurate amount oflight and so the amplitude of response can also be assessed.Conventionally, by contrast, only latency of response is measured. Thus,the present system allows for the assessment of any electrical activityof the retina, so that the activity of the visual areas of the brain canbe assessed.

The measurements made possible with the present system can be of staticsamples or of continuous samples in real time.

Thus, the present invention provides a simple, yet effective way ofensuring that spectrophotometric analysis of a subject can be effectedby aligning the light used so that it passes through the centre of thepupil(s) of the subject's eye(s) to provide a Maxwellian view. Thisensures that the spectrophotometric measurements made can be accurateand that potential injury, that could otherwise ensue, to the subject'siris(es) and other eye structures is avoided.

1. A device for use in non-invasive monitoring of a human or animalsubject's bodily functions in vivo, comprising: a first optical systemfor identifying the centre of a pupil of an eye of the subject, saidfirst system comprising: a first light source for directing lighttowards the eye, first receiving means for receiving light reflectedfrom the iris of the eye, and first processing means for determining theposition of the centre of the pupil from the light reflected from theiris; a second optical system comprising: a second light source fordirecting light to a focussing means for focussing light substantiallyin the centre of the plane of the pupil and directing the focussed lightonto the retina of the eye and providing a Maxwellian view of the eye,second receiving means for receiving light reflected from the retina andback through the pupil and for monitoring intensity of at least oneselected wavelength of said reflected light, and second processor meansfor analysing the light reflected from the structures and determining anabsorbance/reflectance characteristic of said retina; and alignmentmeans for aligning the second system with the centre of the pupil asdetermined by the first optical system.
 2. A means as claimed in claim1, wherein the alignment device is controllable either directly by, orindependently of, the subject.
 3. A means as claimed in claim 1, whereinthe alignment device is controllable by use of manually operatedlever(s), button(s), joystick(s) and/or one or more computer mice.
 4. Adevice as claimed in claim 1, wherein the first and second receivingmeans are comprised by a single receiver.
 5. A device as claimed inclaim 1, wherein the first and second processing means are comprised bya single processor.
 6. A device as claimed in claim 1, wherein thedevice is arranged to project an image processed by the first processingmeans onto the retina of said subject, so as to allow the operator to beable to perceive when the position of the centre of the pupil has beendetermined and so be able to operate the alignment means appropriately.7. A device as claimed in claim 1, wherein the device is arranged togather data from either a selected eye or from both eyes of the subject.8. A device as claimed in claim 1, wherein the first light sourcecomprises one or more light emitting diodes.
 9. A device as claimed inclaim 1, wherein the first or second receiving means is comprised of oneor more charge coupled diode cameras.
 10. A device as claimed in claim1, wherein the first optical system is adapted to monitor the locationof the edge(s) of the pupil(s) so as to allow calculation of the centreof the pupil(s) by the first processing means.
 11. A device as claimedin claim 1, wherein the first and second light sources comprise one ormore optical fibre(s) for transmitting light towards the eye(s).
 12. Adevice as claimed in claim 11, wherein the optical fibre(s) are arrangedto function both as a light source and a light receiver.
 13. A device asclaimed in claim 1, wherein the second light source and second receivingmeans are arranged to monitor the intensity of light of a selectedwavelength returning from the retina(s) of the eye(s).
 14. A device asclaimed in claim 1, wherein the second light source and second receivingmeans are arranged to monitor the intensity of light of differentwavelengths returning from the retina(s) of the eye(s), thereby enablingan absorbance/reflectance characteristic of the retina(s) to bedetermined.